Joana Marie C. Cruz, Hayden Yeung, Rana Alzalzalee, Qile Yang, Hannaneh Kabir, Samantha Annaliese McDonough, Xiaoyue Mei, Michael J. Conboy, Irina M. Conboy
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引用次数: 0
Abstract
Exercise and diet are the best-known methods for attenuating aging-related health decline. However, exercise in older age has diminished gains of strength and agility, and a danger of unrepaired muscle damage. Improving the understanding of age-related differences in response to exercise, our results demonstrate that in old mice, downhill treadmill (eccentric) exercise causes increased influx of CD45+ cells (inflammation) and fibrotic index (fibrosis) in the heart and skeletal muscles. To explain these changes, we identified newly synthesized proteins through bio-orthogonal noncanonical amino acid tagging (BONCAT) and established that exercise exacerbated age-associated protein patterns through a dysregulated transforming growth factor (TGF)-β, Ras/MAPK/PI3Akt, and JAK/STAT pathways. Testing causality, we found that an inhibitor of TGF-β (Alk5 inhibitor, A5i) in combination with the age-diminished peptide oxytocin, previously shown to rejuvenate muscle and brain in sedentary animals, allowed aged mice to exercise without pathologies of skeletal and heart muscles and youthfully restored their de novo proteomes.
期刊介绍：
The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.
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